Hepatic Binding Protein (HBP), a receptor specific for asialoglycoproteins present on the cell-surface of hepatocytes, has already been shown to cause blastogenesis and mitogen-induced cellular cytotoxicity (MICC) in human, desialylated lymphocytes (DL). Since DL accumulate selectively in the liver after iv infusion, it has been postulated that HBP mediates this uptake and could result in MICC against hepatic tissue. The aims of this project are to study in mice: a) the mechanism(s) mediating hepatic accumulation of splenic DL, and b) the effect of DL on hepatic biochemical tests and histology. Hepatic accumulation of DL will be assessed by comparing the proportion of radiolabeled DL and control cells in liver, blood, spleen, and kidney. The mechanism(s) of accumulation will be studied using in situ liver perfusion. DL and control cells will be perfused in serum-free medium after pre-incubation with medium alone, fresh or heat inactivated serum, or Fab fragments of mouse Ig to determine whether hepatic uptake is mediated by HBP or involves Fc or C3b receptors on sinusoidal cells. The latter receptors may participate since mammalian serum contains natural IgM and IgG antibodies which bind to DL. Hepatic biochemical tests and histology will be assessed serially in mice injected intravenously with varying quantities of DL and control cells. Subpopulations of spleen cells, isolated by counterflow centrifugation and complement-mediated lytic depletion will be studied. Histology will be graded in a blind fashion, using specific criteria, and the relationship of DL to hepatocytes and sinusoidal cells assessed by electron microscopy. Since sinusoidal cells may prevent contact between DL and hepatocytes bearing HBP, studies will be performed in the presence of reversible toxic injury, produced zonally with CCl4 or allyl alcohol or diffusely with galactosamine, to disrupt the sinusoidal lining. Immunofluorescence of frozen sections of liver will be used to detect cell-surface antigens unique for lymphocytes from donors and recipients in order to assess the contribution of donor DL to any inflammatory infiltrates.